Dichloromethane → 6-Methyl-5-(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)nicotinic Acid

HRID 335303Notes

Reaction equation

HRID 335303 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([N:8]=[CH:9][C:10]=2[C:11]([NH:13][C:14]2[C:15]([CH3:24])=[N:16][CH:17]=[C:18]([CH:23]=2)[C:19]([O:21]C)=[O:20])=[O:12])[CH:7]=1.[CH3:25][N:26]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>COCCOC.O>[CH3:24][C:15]1[C:14]([NH:13][C:11]([C:10]2[CH:9]=[N:8][N:6]3[CH:7]=[C:2]([C:29]4[CH:28]=[N:27][N:26]([CH3:25])[CH:30]=4)[CH:3]=[CH:4][C:5]=23)=[O:12])=[CH:23][C:18]([C:19]([OH:21])=[O:20])=[CH:17][N:16]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 71282967Methyl 5-(6-bromopyrazolo[1,5-a]pyridine-3-carboxamido)-6-methylnicotinate

Product 1

HCID 712833496-Methyl-5-(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)nicotinic Acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 5-(6-bromopyrazolo[1,5-a]pyridine-3-carboxamido)-6-methylnicotinate (step 1) (7 g, 17.99 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (4.49 g, 21.58 mmol) and cesium carbonate (23.44 g, 71.9 mmol) were stirred in 1,2-dimethoxyethane (60 ml) and water (25.00 ml). The mixture was degassed thoroughly refilling with nitrogen. PdCl2(dppf).CH2Cl2 adduct (0.350 g, 0.429 mmol) was added and the mixture was degassed thoroughly refilling with nitrogen, The mixture was stirred at 100° C. for 7 hrs and then cooled to 50° C. and filtered through glass-fiber paper. The filtrate was acidified to pH 5 by the addition of 2M HCl and filtered. The foam residue was dissolved in DCM/MeOH (1:1) and azeotroped with toluene (×2). The resulting solid was dried in a vacuum oven to afford the title compound;

Workup

  1. customThe mixture was degassed thoroughly
  2. customthe mixture was degassed thoroughly
  3. temperaturecooled to 50° C.
  4. filtrationfiltered through glass-fiber paper
  5. additionThe filtrate was acidified to pH 5 by the addition of 2M HCl
  6. filtrationfiltered
  7. dissolutionThe foam residue was dissolved in DCM/MeOH (1:1)
  8. customazeotroped with toluene (×2)
  9. customThe resulting solid was dried in a vacuum oven

Sources & evidence

ORD record
ord-6fb19a769cd74750b26af5bf58535f52
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Reaction notes

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